Kaufman K M, Sodetz J M
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208.
Biochemistry. 1994 May 3;33(17):5162-6. doi: 10.1021/bi00183a020.
Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact to form the cytolytic C5b-9 complex on target cells. It contains three subunits (C8 alpha, C8 beta, C8 gamma) which are encoded in separate genes. In relation to other proteins of the complement system, C8 gamma is unusual in that it is not structurally related to any other component nor does it have an obvious function. Based on weak but significant sequence similarity, it is proposed to be a member of the lipocalin family of widely distributed proteins that bind and transport small hydrophobic ligands. In this study, the human C8 gamma gene has been characterized and found to contain seven exons spanning approximately 1.8 kb. S1 nuclease and anchored PCR were used to identify the transcription initiation site. This site is preceded by putative regulatory elements that include two SP1 binding sites, several glucocorticoid response elements, and two SV40 enhancer core consensus sequences. A comparison to genes of other lipocalins reveals a remarkably close correlation in exon number, lengths, and phases. A close correspondence in exon boundaries is also observed and suggests that C8 gamma contains the same discrete structural elements that define the characteristic beta-barrel shape of the lipocalins. These results establish that C8 gamma is indeed ancestrally related to the lipocalin family and strengthens the likelihood that its role in the complement system is to bind an as yet unidentified ligand.
人C8是五种补体成分（C5b、C6、C7、C8、C9）之一，这些成分相互作用，在靶细胞上形成溶细胞性C5b-9复合物。它包含三个亚基（C8α、C8β、C8γ），分别由不同的基因编码。与补体系统的其他蛋白质相比，C8γ不同寻常之处在于，它在结构上与任何其他成分都没有关联，也没有明显的功能。基于微弱但显著的序列相似性，它被认为是脂钙蛋白家族的成员，该家族是广泛分布的蛋白质，可结合并转运小的疏水性配体。在本研究中，已对人C8γ基因进行了表征，发现它包含七个外显子，跨度约为1.8 kb。使用S1核酸酶和锚定PCR来鉴定转录起始位点。该位点之前有推定的调控元件，包括两个SP1结合位点、几个糖皮质激素反应元件和两个SV40增强子核心共有序列。与其他脂钙蛋白基因的比较显示出在外显子数量、长度和相位上有非常密切的相关性。在外显子边界也观察到密切对应，这表明C8γ包含相同的离散结构元件，这些元件定义了脂钙蛋白特有的β-桶状结构。这些结果证实C8γ确实在进化上与脂钙蛋白家族相关，并增强了其在补体系统中的作用是结合尚未确定的配体的可能性。
